Grant: Project Grant

Our bodies may appear perfectly symmetrical from the outside, but internally, our organs are arranged asymmetrically in ways that are essential for their proper function. About 1 in every 10,000 children is born with a condition called a laterality defect, in which this left-right organization of organs is disrupted. These defects can lead to serious problems-such as an abnormally looping heart, blocked bile ducts, or a misplaced spleen-that often require lifelong care. The process that establishes left-right differences begins very early in development. Previous studies have identified around 40 genes involved in this process, many of which are linked to key cell signaling pathways and tiny hair-like structures on the cell called cilia. However, these genes account for only 15-20% of lateralit defects, leaving the majority of cases unexplained. Recent research suggests that another group of proteins, known as actomyosin regulators, may also play a crucial role. These proteins control cell movement and shape and are essential for establishing left-right differences in many organisms-yet they have not been studied as extensively as cilia. In our project, we will take advantage of the genetic tractability and short lifespan of the tiny worm Caenorhabditis elegans to investigate how actomyosin proteins establish left-right organization during development. By combining genetic, cell biological, and biophysical approaches, we aim to identify new genes and uncover the mechanisms by which a cell's inherent "handedness" is generated and translated into the large-scale organization of the body. Ultimately, this research may help explain cases of laterality defects that remain a mystery today.